The broad aim of this research is to measure the rates at which gases, ions and un-ionized molecules involved in respiratory exchanges move between the red cell interior and environment, in man and animals, in health and in disease. A more distant goal is to determine if any particular exchange is rate limiting and if this rate can then be used to make measurements of the capillary bed in vivo. A major portion of the work will involve the application of rapid-reaction apparatus, stopped-flow and continuous flow, using PCO2, pH and PO2 electrodes as well as spectrophotometry for analysis, to study fast exchanges of red blood cells. We will extend measurements of red cell permeability to bicarbonate and Cl- and refine a mathematical description of the time course of exchanges within the blood during O2 and CO2 transport. We will extend our measurements of intracellular carbonic anhydrase activity to the fetus and newborn and to patients with a variety of disease conditions. We will extend our measurements of carbamate formation in red cells, plasma and in tissue cells using the stopped-flow rapid pH method. We expect to carry out an extended series of studies on the time required for venous blood pH to reach equilibrium after leaving tissues. We will enlarge our studies of anion binding by hemoglobin to include pertinent anions such as 2,3 DPG and chromate in addition to Cl-. We will continue to explore the 18O2 space of tissues, particularly heart, brain and muscle, and determine if this method can be used to estimate tissue PO2.